(+)-Metheamphetamine ((+)METH) abuse is a chronic, relapsing brain disease, which has imbedded biological social and behavioral components. Unfortunately, there are no medicines for treatment of the biological components of this illness. In particular,, long-lasting medications that could minimize the need for day-to-day patient compliance are sorely needed. We hypothesize that antibody-based medications with their extremely favorable pharmacokinetic properties and unique mechanisms of action might provide new hope as novel medications for a disease process, which in the past has had very limited treatment options. The goal of this component of t he program project is to test the hypothesis that antibody-based medications are effective in the treatment of medical problems associated with (+)METH abuse. Spontaneous locomotor activity, hemodynamic and temperature effects, and pharmacokinetic measurements in animal models of the human disease process will be used to determine the dose-response and concentration-effect relationships involved in the reduction of (+)METH- induced stimulant effects by anti-(+)METH monoclonal antibodies. In addition, the efficacy, duration of action and safety of anti-(+)METH antibodies in the treatment of (+)METH-induced stimulant effects in animal models of recidivism will be assessed. Finally, the efficacy, duration of action and safety of anti-(+)METH antibodies in the treatment and reduction of (+)METH-induced stimulant effects in animal models during continuous, high dose (binge) (+)METH use will be assessed. These studies will utilize animal models that encompass a wide spectrum of the dangerous consequences of (+)METH use, including acute effects of individual doses, effects of large chronic doses that simulate "binge usage", and medical complications that can occur with any pattern of usage. The knowledge gained from these preclinical studies will be used to determine the clinical scenarios in which the medications could be beneficial, and the data set collected in these studies will be used as a first step toward FDA-approved clinical trials.